Susan H. Busch is an associate professor in the Department of Health Policy and Management at Yale University. Ezra Golberstein is an assistant professor in the Division of Health Policy and Management
and the Minnesota Population Center at the University of Minnesota. Ellen Meara is an associate professor in the Dartmouth Institute for Health Policy and Clinical Practice and a Faculty Research Fellow at the
National Bureau of Economic Research. This work was supported by funding from the National Institutes of Health grants R01 MH 080883, K01 DA019485, R01 DA030391, 5T32 MH0119733, and 5R24HD041023
and the Harvard Center for the Developing Child. This research benefi tted from the helpful comments and suggestions from Catherine Fullerton, Nora Gordon, Jon Skinner, Erzo Luttmer, Anthony LoSasso, several
anonymous referees, and from seminar participants at Yale University, Harvard University, University of Minnesota, Dartmouth College, the University of Michigan, the University of Chicago, the NBER Health
Care Meetings, the 2011 American Economic Association Meetings, and the 2012 Midwest Health Econom- ics Conference. The main NSDUH data used in this article can be obtained January 2015 through December
2017 from Ezra Golberstein, Division of Health Policy and Management, University of Minnesota School of Public Health, 420 Delaware St. SE, MMC 729, Minneapolis, MN 55455; email: egolberumn.edu.
[Submitted November 2012; accepted June 2013] ISSN 0022- 166X E- ISSN 1548- 8004 © 2014 by the Board of Regents of the University of Wisconsin System
T H E J O U R N A L O F H U M A N R E S O U R C E S • 49 • 3
The FDA and ABCs
Unintended Consequences of Antidepressant Warnings on Human Capital
Susan H. Busch Ezra Golberstein
Ellen Meara
Busch, Golberstein, and Meara
A B S T R A C T
Using annual cross- sectional data on over 100,000 adolescents aged 12–17, we studied academic and behavioral outcomes among those who
were and were not likely affected by FDA warnings regarding the safety of antidepressants. Compared to other adolescents, adolescents with probable
depression experienced a relative decline in grade point average of 0.14 points following the FDA warnings. The FDA warnings also coincided with
increased delinquency, use of tobacco, and use of illicit drugs. Together, our results stress the importance of mental health and its treatment as an input
into cognitive and noncognitive aspects of human capital.
I. Introduction
A burgeoning theoretical and empirical literature argues that compared with cognitive aspects of human capital that raise individual productivity, “noncogni-
tive” aspects of human capital are equally important. Empirical evidence links varied noncognitive characteristics, ranging from measured hyperactivity, anxiety, locus of
control, and self- esteem in childhood to later wages, income, and social outcomes Blanden, Gregg, and Macmillan 2006; Borghans et al. 2008; Bowles, Gintis, and
Osborne 2001; Currie and Stabile 2009; Heckman, Stixrud, and Urzua 2006. A uni- versally agreed upon construct of noncognitive dimensions of human capital is not yet
available, and researchers currently describe these in a variety of ways. For example, Currie and Stabile 2009 argue that noncognitive aspects of human capital “are likely
to capture some aspects of mental health as well as innate character traits” for in- stance, being extroverted.
An important gap in this promising strand of literature is a full understanding of whether the deleterious effects of mental disorders on human capital are malleable
when addressed through policy or clinical intervention. In the last several decades, innovations in pharmaceutical and behavioral treatments for mental health condi-
tions have drastically altered the treatment of emotional and behavioral problems in children. This paper exploits a dramatic change in treatment of a common condi-
tion during adolescence—that is, depression—to examine how the condition and its treatment affect a broad set of human capital measures including academic outcomes,
delinquency, and substance use.
By age 18, an estimated 15 percent of U.S. children will have experienced some type of depression Merikangas et al. 2010.
1
In adults, depression is associated lower rates of employment and lower earnings among individuals who do work Ettner,
Frank, and Kessler 1997. In adolescents, depression is associated with lower human capital investment. Berndt et al. 2000; Ding et al. 2009; Fletcher 2008. In addition to
its effect on mood, depression causes restlessness, anxiety, diffi culty with concentra- tion, and feelings of worthlessness, all of which may inhibit academic performance
or other aspects of human capital. However, depression’s effect on human capital is diffi cult to measure due to omitted variable biases, described in more detail below.
Hence, regulatory activities that altered the use of antidepressants offer a unique op- portunity to learn about depression and its treatment.
In May of 2003, the manufacturer of Paxil, a popular antidepressant generically known as paroxetine, notifi ed the Food and Drug Administration FDA that parox-
etine increased suicidal thoughts and actions in some pediatric clinical trial partici- pants. The FDA responded with a series of actions including public communications
regarding the safety of paroxetine, public hearings regarding evidence on the safety of all antidepressants, and, ultimately, the October 2004 decision to require black- box
warnings regarding the safety of pediatric antidepressant use on virtually all anti- depressant product labels and packaging.
The evidence to date, described below in detail, demonstrates that the FDA’s re- lease of this new safety information was widely covered in the popular press Barry
and Busch 2010, and accompanied abrupt declines in pediatric and adolescent anti- depressant use of 20–30 percent following years of steady increases in pediatric and
adolescent antidepressant use Busch et al. 2010; Gibbons et al. 2007; Libby et al.
1. In addition to mood and suicidal thoughtsactions, the Diagnostic and Statistical Manual of Mental Dis- orders-Fourth Edition’s diagnosis of depression includes changes in: sleep, eating, energy, concentration,
and self-image.
2007; Nemeroff et al. 2007; Olfson, Marcus, and Druss 2008; Rosack 2005. During the period immediately before and after the FDA warnings on antidepressants, the
extensive margin of treatment seeking any treatment versus none did not change measurably, as we describe below. However, care along the intensive margin the total
treatment delivered to those treated fell as patients were less likely to receive anti- depressants, and no evidence suggests any substantial replacement of antidepressant
therapy with behavioral therapies like counseling. Throughout the paper, we refer to this movement along the intensive margin from treatments that include an anti-
depressant to those that do not as a decline in treatment. Critics of the FDA warn- ings expressed concerns regarding the impact of the warnings on clinical outcomes.
These concerns increased when youth suicide rates climbed abruptly in 2004 and 2005, following a decade of relatively steady decline Bridge et al. 2008; Gibbons
et al. 2007.
To examine the effects of treated and untreated adolescent depression on human capital outcomes, we exploit the abrupt change in pediatric antidepressant use induced
by FDA warnings to compare outcomes of adolescents who sought professional help for depression problems just before and just after the release of the FDA advisories
in 2004. This unique natural experiment permits us to examine several questions with relevance for the economics of human capital, for health policy, and for clinical prac-
tice. First, it allows us to study potential unintended consequences of a regulatory policy designed to protect pediatric patients from safety risks of a widely used class of
pharmaceuticals. Second, the FDA’s actions permit us to estimate effects of reducing the pharmaceutical treatment of depression on human capital development in adoles-
cents. Third, we compare the effects of depression problems among adolescents more and less likely to receive antidepressants in a real world setting rather than the more
pristine setting of clinical trial research.
Using seven years of the annual cross- sectional National Survey on Drug Use and Health 2001–2007, we use a difference- in- difference design to study academic and
behavioral outcomes in over 100,000 adolescents aged 12–17, comparing outcomes for adolescents with and without a recent episode of probable depression. Compared
to other adolescents, adolescents with probable depression experienced a relative de- cline in grade point average GPA of 0.14 points after heightened FDA attention to
the safety of antidepressants, and changes in average GPA for depressed adolescents were driven entirely by declines among adolescent girls. We fi nd no change in average
grades among adolescents without recent episodes of probable depression. We also fi nd similar patterns for substance use and delinquency outcomes for adolescents with
probable depression, relative to other adolescents. We do not fi nd any evidence that our results are explained by compositional changes in the group of adolescents with
probable depression.
The paper proceeds as follows: Section I provides background on the FDA actions surrounding antidepressant use in pediatric patients and media coverage of FDA an-
nouncements, advisories and warnings; Section II describes changes in prescribing patterns and youth suicides surrounding the 2003 and 2004 FDA actions; Section III
explains the data and methods in detail; Section IV presents our regression analyses for academic outcomes, substance use, and delinquency; Section V discusses potential
threats to our approach; and Section VI concludes.
II. FDA Activity on the Safety of Pediatric Antidepressant Use
